Human Immunodeficiency Virus Infections
Conditions
Brief summary
The hope of this study is to gather data and information about the tolerability and effectiveness of Lexiva versus Sustiva in patients who have have been generally underrepresented in clinical trials.
Detailed description
The objective of this study is to gain tolerability and efficacy data for Norvir-boosted Lexiva versus Sustiva, both used in combination with Epzicom, as components of a first-line, once daily regimen for the treatment of HIV-1 infection in a patient population that is underrepresented in US clinical research.
Interventions
DRUGEfavirenz 600mg
QD regimen of Sustiva (efavirenz 600 mg) + Epzicom (abacavir 600 mg / lamivudine 300 mg) The intervention may be switched for the following reasons: * To resolve a Grade 3 or 4 Adverse Event * The subject experienced a virologic failure (as defined in section 3.6.2) * The investigator believes the subject is at a significant risk for failing to comply with the protocol AND the investigator believes a regimen substitution is likely to resolve the compliance issue * The investigator believes there is any other significant safety concern for the subject associated with remaining on the current regimen (e.g., hypersensitivity reaction, increased risk of suicide)
DRUGBoosted Lexiva
Once daily (QD) regimen of Lexiva (fosamprenavir 1400 mg) + Norvir (ritonavir 100 mg) + Epzicom (abacavir 600 mg / lamivudine 300 mg) The intervention may be switched for the following reasons: * To resolve a Grade 3 or 4 Adverse Event * The subject experienced a virologic failure (as defined in section 3.6.2) * The investigator believes the subject is at a significant risk for failing to comply with the protocol AND the investigator believes a regimen substitution is likely to resolve the compliance issue * The investigator believes there is any other significant safety concern for the subject associated with remaining on the current regimen (e.g., hypersensitivity reaction, increased risk of suicide)
Sponsors
GlaxoSmithKline
Georgetown University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Screening plasma HIV-1 RNA viral load \>5000 copies/mL Self-identification as having any non-White/Caucasian European geographic ancestry (i.e., an individual is eligible if she/he does not have any White/Caucasian European ancestry; OR an individual is eligible if she/he indicates a mix of White/Caucasian European ancestry AND one or more other geographic ancestries); Antiretroviral-naïve (no treatment with any antiretroviral drug in the 28 days prior to study entry and ≤14 days of treatment ever with any antiretroviral drug) Negative test for the HLA-B\*5701 allele Ability and willingness to give written informed consent Either gender is eligible, but enrollment of at least two female subjects to every one male subject is strongly encouraged. A female subject is eligible to participate in the study if she is of: 1. Non-childbearing potential or, 2. Childbearing potential with a negative pregnancy test at screen and agrees to use one of the following methods of contraception: i. Agreement for complete abstinence from intercourse from 2 weeks prior to administration of investigational products, throughout the study, and for 2 weeks after discontinuation of all study medications; ii. Double barrier contraception (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide); iii. Any intrauterine device (IUD) with published data showing that the expected failure rate is less than 1% per year (not all IUDs meet this criterion); iv. Any other method with published data showing that the lowest expected failure rate for the method is less than 1% per year. v. Sterilization (female subject or male partner of female subject)
Exclusion criteria
Screening HIV-1 genotype indicating the presence of any of the following mutations in the reverse transcriptase (RT) region: K65R, L74V, K103N, Y115F, Y181C/I, Y188C/L/H or G190S/A, or a combination of two or more thymidine analog mutations (M41L, D67N, K70R, K219Q or E) that include changes at either L210 or T215, associated with resistance to abacavir, lamivudine, or efavirenz; OR within the protease region, detection of any of the following mutations associated with resistance to fosamprenavir or ritonavir: I50V, I54L/M, I84V, or the combination of the two mutations V32I+I147V Positive for Hepatitis B surface antigen (HBsAg+) Requirement for active treatment for hepatitis C virus infection, as indicated by both a positive Hepatitis C Virus serology AND either: 1. Decompensated liver disease, or 2. Aspartate aminotransferase (AST) \>3X the upper limit of normal (ULN), or 3. Alanine aminotransferase (ALT) \>3X the ULN Currently pregnant, intending to become pregnant during the study period, or breast-feeding Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), any vaccinations, systemic cytotoxic chemotherapy, or investigational therapy within 28 days prior to study entry. Chronic treatment with prednisone at a daily dose of 10 mg or less is permitted. Acute treatment (less than 21 days) with larger doses of corticosteroids for acute therapy is permitted. Active or suspected drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements Judged by the investigator to be at significant risk of failing to comply with the provisions of the protocol as to cause harm to self or seriously interfere with the validity of the study results Active or acute Centers for Disease Control Clinical Category C event at screening. (Note: Treatment for the acute event must have been completed at least 28 days prior to screening.) Clinically relevant pancreatitis or clinically relevant hepatitis at screening Hgb\<8g/dl, platelet count \<50,000/mm3, calculated creatinine clearance \<50ml/min via Cockroft-Gault equation, or AST or ALT \> 5X the ULN Any Grade 4 laboratory abnormality
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Needing to Switch Comparator Drugs (FPV/r or EFV) | 96 weeks | Subjects were randomized and initiated treatment on one of the antiretroviral arms(FPV/r or EFV) at study Entry visit. Subjects would be switched for the follwing reasons: * To resolve a Grade 3 or 4 Adverse Event * The subject experienced a virologic failure (as defined in section 3.6.2) * The investigator believes the subject is at a significant risk for failing to comply with the protocol AND the investigator believes a regimen substitution is likely to resolve the compliance issue * The investigator believes there is any other significant safety concern for the subject associated with remaining on the current regimen (e.g., hypersensitivity reaction, increased risk of suicide) |
| Number of Subjects Developing Any Treatment-related Grade 3-4 Adverse Events | 96 weeks | — |
Countries
United States
Participant flow
Recruitment details
Patients ≥18 years of age who were ART-naïve (≤14 days of treatment with any ART agent), HLA-B\*5701-negative, and had a screening HIV-1 RNA \>5000 copies/mL. Patients were required to be of minority race or ethnicity; white, non-Hispanic patients were not eligible for this study.
Participants by arm
| Arm | Count |
|---|---|
| Once Daily (QD) Regimen of Lexiva Once daily (QD) regimen of Lexiva (fosamprenavir 1400 mg) + Norvir (ritonavir 100 mg) + Epzicom (abacavir 600 mg / lamivudine 300 mg). | 51 |
| QD Regimen of Sustiva QD regimen of Sustiva (efavirenz 600 mg) + Epzicom (abacavir 600 mg / lamivudine 300 mg) | 50 |
| Total | 101 |
Baseline characteristics
| Characteristic | QD Regimen of Sustiva | Once Daily (QD) Regimen of Lexiva | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 50 Participants | 50 Participants | 100 Participants |
| Age Continuous | 34 years STANDARD_DEVIATION 2 | 33.5 years STANDARD_DEVIATION 2 | 34 years STANDARD_DEVIATION 2 |
| Region of Enrollment United States | 50 participants | 51 participants | 101 participants |
| Sex: Female, Male Female | 16 Participants | 16 Participants | 32 Participants |
| Sex: Female, Male Male | 34 Participants | 35 Participants | 69 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 51 | 15 / 50 |
| serious Total, serious adverse events | 2 / 51 | 2 / 50 |
Outcome results
Primary
Number of Subjects Developing Any Treatment-related Grade 3-4 Adverse Events
Time frame: 96 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Once Daily (QD) Regimen of Lexiva | Number of Subjects Developing Any Treatment-related Grade 3-4 Adverse Events | 2 participants |
| QD Regimen of Sustiva | Number of Subjects Developing Any Treatment-related Grade 3-4 Adverse Events | 3 participants |
Primary
Number of Subjects Needing to Switch Comparator Drugs (FPV/r or EFV)
Subjects were randomized and initiated treatment on one of the antiretroviral arms(FPV/r or EFV) at study Entry visit. Subjects would be switched for the follwing reasons: * To resolve a Grade 3 or 4 Adverse Event * The subject experienced a virologic failure (as defined in section 3.6.2) * The investigator believes the subject is at a significant risk for failing to comply with the protocol AND the investigator believes a regimen substitution is likely to resolve the compliance issue * The investigator believes there is any other significant safety concern for the subject associated with remaining on the current regimen (e.g., hypersensitivity reaction, increased risk of suicide)
Time frame: 96 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Once Daily (QD) Regimen of Lexiva | Number of Subjects Needing to Switch Comparator Drugs (FPV/r or EFV) | 1 participants |
| QD Regimen of Sustiva | Number of Subjects Needing to Switch Comparator Drugs (FPV/r or EFV) | 2 participants |